We propose to renew the participation of the Midwest Hepatitis B Consortium as a member of the Hepatitis B Research Network (HBRN). The Midwest Consortium consists of three sites: Saint Louis University adult, Saint Louis University pediatric and Washington University adult. The consortium has functioned well and collaboratively in recruiting and enrolling patients in the HBRN studies and its performance compares favorably to that of other network sites, including some of those in much larger cities with many more individuals at-risk for hepatitis B. In addition to their successes in recruiting an enrolling, investigators at each site within the Midwest Consortium brings a special strength to the Network: Thus, Dr. Di Bisceglie (SLU adult) provides experience and leadership, including his role as co-chair of the Ancillary Studies Committee. Dr Teckman (SLU pediatric) is PI of one of only 7 pediatric sites within the network, and Dr Lisker-Melman (Wash. U adult) is positioned to be a major contributor to the separately- funded ancillary study on HIV-HBV co-infection that is being conducted by the Network. The Midwest Consortium is therefore well positioned to continue enrolling patients in the existing studies and also to contribute to the development of new therapeutic studies for the network. Finally, Dr. Di Bisceglie has been very successful is establishing basic research collaborations to enhance the productivity of the Network. Thus, his long-time collaborator, Dr John Tavis is a recipient of a grant supplement to conduct an approved Virology ancillary study aimed at developing RNaseH inhibitors as a novel method of treatment for hepatitis B. This application also includes a proposal from Dr Adam Gehring, an experienced HBV immunologist at SLU which will make use of biorepository specimens to study antiviral effects of various immunomodulators, including GM-CSF. If these studies confirm preliminary observations, they would form the basis for a novel therapeutic approach to be adopted in the next phase of the HBRN in which patients already on long-term antiviral therapy with complete suppression of HBV could receive immunomodulators in an attempt to enhance the rate of HBsAg clearance and to allow patients to stop their antiviral therapy